Glucocorticoid — and non‐glucocorticoid induction of lipocortins (annexins) 1 and 2 in rat peritoneal leucocytes in vivo

Abstract

1 We have studied the occurrence, distribution and disposition of lipocortins (annexins) 1, 2 and 5 in mixed peritoneal leucocytes obtained from rats in which glucocorticoid levels were altered by adrenalectomy, administration of the glucocorticoid antagonist, RU486, or by injection of dexamethasone or hydrocortisone, as well as from rats in which the peritoneal cells were elicited by inflammatory stimuli. 2 In cells obtained from untreated rats with an intact adrenal cortex, lipocortins 1, 2 and 5 were readily detectable: the majority of each of the proteins was apparently located intracellularly with much smaller amounts in the membrane. Lipocortin 1 and to a lesser extent lipocortin 5 were also seen in a Ca2'-dependent association with the external plasma membrane. Following administration of RU486(2 x 20 mg kg-1) the amounts of lipocortin 1 and 2 in cells were greatly reduced. Conversely, injection of hydrocortisone (1 mg kg-') or dexamethasone (0.08 mg kg-1) caused an increase in the amount of lipocortin 1 and 2 in peritoneal cells within 30 min. Lipocortin 5 was unchanged by any manipulation of glucocorticoid levels. 3 Lipocortins 1 and 2 were elevated in both intracellular and membrane-associated fractions of macrophages elicited by intraperitoneal injection in inflammogens. This phenomenon also occurred in adrenalectomized animals. 4 Our data indicate that glucocorticoids control the synthesis of some members of the lipocortin family in rat mixed peritoneal cells but also suggest the existence of a separate system for controlling the generation of this protein. The significance of these observations is considered in relation to the mechanism of glucocorticoid hormone action on eicosanoid production.

An overview of the effects of annexin 1 on cells involved in the inflammatory process

“…The constitutive expression of ANXA1 mRNA and protein by macrophages has been shown reproducibly by many authors to increase following exposure to GC in vitro and in vivo (Ambrose et al 1992, De Caterina et al 1993, Peers et al 1993, Coméra et al 1995, Perretti & Flower 1996, Yang et al 1998, Hall et al 1999.…”

“…ANXA1 has been shown to be expressed by many different tissue specific macrophages including alveolar (Ambrose et al 1992, De Caterina et al 1993, peritoneal (Peers et al 1993), and synovial macrophages (Yang et al 1998) as well as microglial cells (Minghetti et al 1999), suggesting a regulatory role for the molecule in macrophage activity in general, that is not confined to any given tissue type. The constitutive expression of ANXA1 mRNA and protein by macrophages has been shown reproducibly by many authors to increase following exposure to GC in vitro and in vivo (Ambrose et al 1992, De Caterina et al 1993, Peers et al 1993, Coméra et al 1995, Perretti & Flower 1996, Yang et al 1998, Hall et al 1999.…”

Annexin-1 Regulates Growth Arrest Induced by High Levels of Estrogen in MCF-7 Breast Cancer Cells

“…Evidence associating ANXA1 expression and function with glucocorticoid treatment is indisputable (21)(22)(23)28). This induction of ANXA1 expression can be blocked by the glucocorticoid receptor antagonist RU486 (29).…”

“…Its endogenous function is still under debate, but most have focused on its anti-inflammatory actions, shown to mimic those of glucocorticoids (20). ANXA1 is glucocorticoid-inducible (21)(22) through transcriptional activation of the glucocorticoid response element as well as through rapid de novo synthesis (23). Glucocorticoids were not effective in ANXA1-deficient mice in two models of acute inflammation, suggesting that ANXA1 could be the endogenous protein mediating the anti-inflammatory actions of glucocorticoids (24).…”

An Immunocytochemical and In Situ Hybridization Analysis of Annexin 1 Expression in Rat Mast Cells: Modulation by Inflammation and Dexamethasone

“…ANX-1 differs from other members of the annexin family in that it is mainly localized in the cytoplasmic compartment of resting neutrophils and macrophages, but after cell activation it is translocated to the cell-surface (Peers et al, 1993) and extracellular fluids (Vergnolle et al, 1995). Human neutrophils can externalize substantial amounts of the protein (more than 50%) upon adhesion to monolayers of endothelial cells (Perretti et al, 1996b).…”